Troglitazone induction of COX-2 expression is dependent on ERK activation in keratinocytes

Prostaglandins Leukot Essent Fatty Acids. 2006 Mar;74(3):193-7. doi: 10.1016/j.plefa.2005.12.001. Epub 2006 Jan 30.

Abstract

Cyclooxygenase-2 (COX-2) plays an important role in tumorigenesis of several tissues, including skin. We report here that troglitazone, a thiazolidinedione class of antidiabetic drug, induced COX-2 expression at both the protein and mRNA levels and increased production of prostaglandin E2 (PGE2) in cultured keratinocytes. Troglitazone-induced COX-2 expression in keratinocytes was likely peroxisome proliferator-activated receptor gamma (PPARgamma)-independent. Troglitazone treatment of these cells also resulted in a sustained increase in phosphorylation of ERK. We show that induction of COX-2 by troglitazone was almost completely inhibited by specific inhibitors of ERK activation. These data suggest that troglitazone is capable of inducing COX-2 expression through an ERK-dependent mechanism in mouse skin keratinocytes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Cell Line
  • Chromans / pharmacology*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Dinoprostone / metabolism
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Flavonoids / pharmacology
  • Gene Expression / drug effects
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Mice
  • PPAR gamma / agonists
  • PPAR gamma / genetics
  • Peroxisome Proliferator-Activated Receptors / agonists
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Thiazolidinediones / pharmacology*
  • Troglitazone
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Chromans
  • Flavonoids
  • PPAR gamma
  • Peroxisome Proliferator-Activated Receptors
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Thiazolidinediones
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Troglitazone
  • Dinoprostone
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one